Cinacalcet HCl reduces hypercalcemia in primary hyperparathyroidism across a wide spectrum of disease severity.

CONTEXT: Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations. OBJECTIVE: The objective of the investigation was to establish the efficacy of cinacalcet in reducing serum Ca in patients with PHPT across a wide spectrum of disease severity. DESIGN AND SETTING: The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT. PATIENTS: Patients were grouped into three disease categories for analysis based on the following: 1) history of failed parathyroidectomy (n = 29); 2) meeting one or more criteria for parathyroidectomy but without prior surgery (n = 37); and 3) mild asymptomatic PHPT without meeting criteria for either above category (n = 15). INTERVENTION: The intervention in this study was treatment with cinacalcet for up to 4.5 yr. OUTCOMES: Measurements in the study included serum Ca, PTH, phosphate, and bone-specific alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study period. RESULTS: The extent of cinacalcet-induced serum Ca reduction, proportion of patients achieving normal serum Ca (≤10.3 mg/dl), reduction in serum PTH, and increase in serum phosphate were similar across all three categories. Except for decreased aBMD at the total femur indicated for parathyroidectomy group at 1 yr, no significant changes in aBMD occurred. The efficacy of cinacalcet was maintained for up to 4.5 yr of follow-up. AEs were mild and similar across the three categories. CONCLUSIONS: Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated.

Cinacalcet treatment of primary hyperparathyroidism: biochemical and bone densitometric outcomes in a five-year study.

CONTEXT: Primary hyperparathyroidism (PHPT) is characterized by chronically elevated serum calcium and inappropriately normal or increased PTH. OBJECTIVE: Our objective was to evaluate long-term tolerability, safety, and efficacy of cinacalcet in PHPT patients. DESIGN AND SETTING: A 4.5-yr open-label extension study was conducted at 14 study centers in the United States. PATIENTS OR OTHER PARTICIPANTS: Forty-five subjects with PHPT from a double-blind, placebo-controlled, 1-yr trial were continued into this study. INTERVENTIONS: After the parent study, all subjects were treated with 30 mg cinacalcet twice daily, increasing to 50 mg twice daily during the 12-wk titration if serum calcium levels were 10.3 mg/dl or higher and then maintained on cinacalcet for up to 4.5 yr. MAIN OUTCOME MEASURES: Assessments included serum calcium, PTH, phosphate and alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety chemistries and hematology, and adverse events were monitored throughout. RESULTS: Compared with baseline, cinacalcet treatment improved biochemical measures of PHPT including reducing serum calcium and PTH and increasing serum phosphate with slight increases in alkaline phosphatase. No changes in z-scores of aBMD at spine, hip, or wrist were seen with annual percent changes, consistent with reports for untreated postmenopausal women or PHPT patients. Safety biochemistries remained normal, and adverse events (most commonly arthralgia, myalgia, diarrhea, respiratory infection, and nausea) were mild to moderate in severity. CONCLUSIONS: Treatment of PHPT patients with cinacalcet for up to 5.5 yr maintained normocalcemia, reduced plasma PTH, increased serum phosphate and alkaline phosphatase with no significant effects on aBMD, and was well tolerated.